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A Critical Review of the Efficacy and Safety of Inclisiran

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Abstract

The association between low-density cholesterol (LDL-C) and cardiovascular disease (CVD) is well-established, with an emphasis on lowering LDL-C levels to reduce cardiovascular events. Statin therapy has been the traditional treatment for LDL-C reduction, in addition to lifestyle modifications, but studies have shown that a substantial proportion of patients does not reach target LDL-C goals despite receiving maximally tolerated statin medications. Additionally, statin therapy is associated with a few shortcomings as many patients initiated on these medications discontinue treatment within 1 year because of lack of tolerability. Furthermore, guidelines from both the American College of Cardiology and the American Heart Association highlight the importance of obtaining LDL-C goals because of the residual atherosclerotic CVD risk that remains in high-risk populations. That the residual cardiovascular risk remains despite statin therapy highlights the importance of evaluating therapeutic approaches that possess effective lipid lowering that can be used adjunctively with statins. Much focus has been directed towards the proprotein convertase subtilisin/kexin type 9 (PCSK9) pathway, leading to the development of evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9. These agents have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk, but the need for biweekly or monthly subcutaneous injections has generated concerns for patient compliance. A new pathway is being studied in which a synthetic small interfering ribonucleic acid (siRNA) targets the PCSK9 gene expressed in hepatocytes to prevent PCSK9 production. The siRNA, inclisiran sodium, significantly reduces hepatic production of PCSK9, causing a marked reduction in LDL-C levels, and exhibits sustained pharmacodynamic effects when dosed subcutaneously every 6 months. This review presents and discusses the current clinical and scientific evidence pertaining to inclisiran sodium.

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Authors and Affiliations

  1. East Coast Institute for Research, Jacksonville, FL, USA

    Jennifer Hardy, Stephanie Niman, Rushab Choksi & Rebecca F. Goldfaden

  2. Baker-Gilmour Cardiovascular Institute, Jacksonville, FL, USA

    Edward Pereira & Todd Lewis

  3. University of Florida, College of Pharmacy, Jacksonville, FL, USA

    Jessica Reid

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  1. Jennifer Hardy
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  2. Stephanie Niman
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  7. Rebecca F. Goldfaden
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Correspondence to Rebecca F. Goldfaden.

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No external funding was used in the preparation of this manuscript.

Conflict of interest

Jennifer Hardy, PharmD; Stephanie Niman, PharmD; Edward Pereira, MD; Todd Lewis, MD; Jessica Reid, PharmD; Rushab Choksi, PharmD; and Rebecca F. Goldfaden, PharmD, have no conflicts of interest that might be relevant to this manuscript.

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Authors' contributions

All authors contributed to the review. Rebecca Goldfaden had the idea for the article, Stephanie Niman and Jessica Reid performed the literature search and data analysis, and all authors drafted and/or critically revised the review. All authors read and approved the final manuscript.

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Hardy, J., Niman, S., Pereira, E. et al. A Critical Review of the Efficacy and Safety of Inclisiran. Am J Cardiovasc Drugs 21, 629–642 (2021). https://doi.org/10.1007/s40256-021-00477-7

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  • DOI: https://doi.org/10.1007/s40256-021-00477-7

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